Kathleen E. Corey, MD, MPH is a member of the faculty of the Gastrointestinal Division of Massachusetts General Hospital (MGH) and an instructor in medicine at Harvard Medical School (HMS). Dr. Corey has a background in patient oriented research, gastroenterology and hepatology. Her research has focused on the interaction between lipid metabolism and chronic liver disease, specifically hepatitis C and non-alcoholic fatty liver disease (NAFLD). Her work in these areas has resulted in 8 first author publications including the identification of a two lipid biomarkers, oxidized low density lipoproteins (OxLDL) and non-high density lipoprotein cholesterol for NAFLD. In addition, her recent study assessing protective factors for the development of NAFLD, she found that obstructive sleep apnea (OSA) was one of the strongest predictors of normal liver histology in patients with obesity, suggesting that OSA may play a role in NAFLD development. Both OSA and NAFLD are important public health conditions. NAFLD affects 30% of Americans and can lead to cirrhosis and hepatocellular carcinoma. More than 12 million Americans are estimated to suffer from OSA which worsens metabolic disease and increases the risk of cardiovascular disease and sudden death. The study of these conditions and their interactions will lead to new treatment options and improved public heath outcomes. Using knowledge gained from these studies, Dr. Corey's proposal will focus on testing three hypotheses; 1) OSA is associated with an increased prevalence of NAFLD, 2) The interaction between OSA and NAFLD is mediated by lipid peroxidation as measured by OxLDL and 3) Treatment of OSA in patients with NAFLD will improvement in steatosis. While animal studies have found a strong relationship between chronic intermittent hypoxia, the experimental mimic of OSA, and NAFLD, human studies have been limited by methodologic issues leading to inconclusive results. To complete this proposal Dr. Corey will require additional training in study design, statistical analysis and obstructive sleep apnea mechanics. Dr. Corey will benefit from the guidance of her two co-mentors, Dr. Raymond Chung, an established basic and clinical investigator in hepatology and Dr. Atul Malhotra, an established physician-scientist in the study of OSA. Both Drs. Chung and Malhotra have established track records in the mentoring of clinical investigators and both hold NIH K24 awards. Dr. Corey will also receive mentoring from Dr. Steven Grinspoon, an established investigator in metabolic studies and K24 recipient and Dr. Shiva Gautam, an experience biostatistician and mentor. She will receive formal didactic training in study design, advanced biostatistics, and predictive modeling from the Master in Medical Science Program at Harvard Medical School. She will also receive training in OSA pathophysiology through courses at Harvard- Massachusetts Institute of Technology Health Sciences and Technology, lead by her co-mentor, Dr. Malhotra. With this additional education and guidance, as well as the supportive environment provided by the MGH, Dr. Corey will be well poised to complete this proposal and develop into an independent clinical investigator.